Chemically reactive estrogen analogs are being prepared as potential affinity labeling agents for the estrogen receptor or as cytotoxic agents that will be selective for cells containing estrogen receptor. Affinity labeling agents that have high affinity for the estrogen receptor, have low affinity for non-receptor binding proteins, and are capable of reacting efficiently with the estrogen receptor, either through an electrophilic or a photoreactive function, are being synthesized. These agents will be used to label the uterine cytosol estrogen receptor, and the labeled receptor will be characterized carefully. The cytotoxic estrogens will be assayed in cell culture systems with estrogen-responsive and non-responsive cells. Antiestrogens and antiestrogen metabolites will be prepared in high specific activity, tritium-labeled form. Their interaction with the estrogen receptor in vitro and in vivo will be investigated in an attempt to discern differences between receptor complexed with agonists vs antagonists.